This invention relates to miniaturized drug delivery devices and more particularly, to controlled time and rate release multi-welled drug delivery devices.
The efficacy of many drugs is directly related to the way in which they are administered. A wide variety of methods for controlled release have been developed, including pumps, patches, tablets, and implants. However, all of these methods have unique disadvantages when considering the treatment of a chronic condition. A major disadvantage of both external and internal micropumps is that they depend on the reliable operation of moving parts. Failure of the pump due to breakage, leakage, or clogging may be catastrophic for the individual. Patches are useful only for certain chemicals that may be absorbed through the skin. Tablets are widely used but can achieve release for only a limited amount of time before they pass through the digestive system. Many polymeric materials proposed to be used for pulsatile release of a chemical are responsive to changes in pH or temperature (Lee, et al., J. Appl. Polym. Sci., 62:301–11 (1996)), the application of ultrasound (Kost, et al., Proc. Nat. Acad. Sci., USA, 86:7663–66 (1989); Levy, et al., J. Clin. Invest., 83:2074–78 (1989)), changes in enzymes, or changes in electric (Kwon, et al., Nature, 354:291–93 (1991)) or magnetic (Kost, et al., J. Biomed. Mater. Res., 21:1367–73 (1987)) fields. These polymeric systems are limited to the release of only one or a few chemicals, and may need to be tailored to the specific condition which they are to treat (glucose-sensitive insulin release systems for the treatment of diabetes, for example (Kitano, et al., J. Control. Release, 19:162–70 (1992))). Additionally, the stimuli source may be large, expensive, or too complex for frequent use. Moreover, fabrication procedures for implants such as microspheres are usually complex, and the solvents or heat used during fabrication can adversely affect the stability of the drugs contained in the microspheres.
U.S. Pat. No. 5,797,898 and U.S. Pat. No. 6,123,861, to Santini, et al., describe active and passive microchips for drug delivery. However, the fabrication methods described therein are primarily based on standard microelectronics processing techniques. It would be advantageous to provide additional, preferably simple and inexpensive, methods of manufacturing such microchip devices. It would also be advantageous to develop new methods of triggering and controlling release of the molecules.
PCT WO 99/03684 discloses a process of making a device having a surface microstructure of wells or channels using a low cost process of screen printing a curable or polymerizable material onto a plastic substrate and then curing or polymerizing the material. The device can contain hundreds of wells and be used as a microtitre plate array, holding reagents of interest, but it is not designed to provide any sort of controlled release or delivery function.
It is therefore an object of the present invention to provide a variety of techniques for the manufacture, particularly the low cost manufacture, of multi-welled microchip devices for the controlled release of drugs and other molecules.
It is another object of the present invention to provide a device that allows delivery of drugs or other molecules in either a pulsatile or continuous manner, using a variety of materials of construction and methods for triggering and controlling release of the molecules.